mnsod (esophageal protectant) to prevent esophagitis during radiation/chemotherapy treatment for non-small cell lung cancer (nsclc)

Conditions: Esophageal; Toxicity

Summary: this is a phase i-ii study evaluating the feasibility, safety, and efficacy of swallowed mnsod plasmid/liposome (pl) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (nsclc).

this is a phase i-ii study evaluating the feasibility, safety, and efficacy of swallowed mnsod plasmid/liposome (pl) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (nsclc). phase i of the study will assess the feasibility and safety of mnsod pl by dose escalation in 3 cohorts of 3 chemoradiotherapy subjects each (cohort1 = 0.3 mg/dose, cohort2 = 3 mg/dose, cohort3 = 30 mg/dose). the highest dose completed (as determined by toxicity monitoring for 8 weeks from initial treatment) will be the starting dose for phase ii. phase ii will examine the efficacy of mnsod pl by assessing the incidence of grade 3 or 4 esophagitis in 27 additional chemoradiotherapy subjects. incidence of esophageal toxicity, as well as clinical response to the combination of chemoradiotherapy with mnsod pl are the outcomes of interest.

Eligibility criteria:
inclusion criteria: * histologically or cytologically documented nsclc including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas) and poorly differentiated non-small cell lung cancer. totally resected tumors are excluded. * subjects must be without evidence of m0. * subjects with t1 or t2 disease with n2 or tumor stage 3, lymph node metastasis 1-2 ( stage 1) disease (stage iiia) are eligible if they are medically inoperable. subjects with t4 with any n or any t with n3 disease are eligible. radiographic evidence of mediastinal lymph nodes \>2.0 cm in the largest diameter is sufficient to stage n2 or n3 disease. if the largest mediastinal node is \< 2.0 cm in diameter and this is the basis for stage iii disease, then at least one of the nodes must be proven positive cytologically or histologically. * subjects with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. the boost volume must be limited to \< 50% of the ipsilateral lung volume. * subjects with a pleural effusion that is a transudate, cytologically negative and non-bloody are eligible if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy. exudative, bloody, or cytologically malignant effusions are ineligible. if a pleural effusion can be seen on the chest ct but not on chest x-ray and is too small to tap, the subject will be eligible. * subjects must be deemed a suitable candidate for protocol treatment by both radiation oncology and medical oncology * subjects must have a performance status \> 70 (karnofsky performance scale). * subjects weight loss \< 10% in 3 months prior to diagnosis. * subjects must be male or female \> 18 years. * subjects must have had no prior systemic chemotherapy, radiation therapy to the thorax, or total surgical resection. * at least 3 weeks since formal exploratory thoracotomy and the subject has recovered from surgery, or 1 week from diagnostic thoracoscopy. * laboratory values must be as follows: (see section 6.1 of the full protocol for required timing): granulocytes \> 2,000/ml, platelets \> 100,000/ml, hemoglobin\* \> 8 mg/dl, bilirubin \ 50 ml/n (24 hour or calculated, forced expiratory volume at one second \> 800 cc. note: \*physician can maintain a subject's hemoglobin with the use of erythropoetin or transfusions prophylactic use of g-csf (colony stimulating factor, is not permitted). * subjects must have a mri or ct brain scan within 4 weeks prior to study entry to rule out asymptomatic brain metastases. * subjects must be informed of the investigational nature of the study and sign an informed consent form and have no serious medical or psychiatric illnesses that would prevent informed consent. * no history of serious cardiac disease that is not adequately controlled. * female subjects must be non-pregnant and non-lactating. female subjects of childbearing potential must implement an effective method of contraception during the study. all women of childbearing potential must have a pre-study negative serum or urine pregnancy test within 7 days prior to study entry. exclusion criteria * inability to meet any of the above eligibility requirements

Keywords: nsclc lung cancer chemotherapy radiation therapy radiation toxicity